This is a research study for advanced prostate cancer. An experimental drug called AN-152 (also known as AEZS-108) will be used. The purpose of this study is to test the safety, tolerability and benefits of an experimental drug called AN-152.

The participants tumor will be tested for expression of this receptor (using an old biopsy). If the participants cancer does not have this receptor, participants will not be eligible to participant in this study.

AN-152 (AEZS-108) is administered intravenously (IV) over 2 hours and will be given at the specified dose every 3 weeks. Premedication with dexamethasone 8mg is recommended.

Participants will continue treatment until death, disease progression, unacceptable toxicity, participants refusal, treatment delay >3 weeks, or the completion of 6 cycles. Continuation beyond 6 cycles is left at the discretion of the study doctor.

The study is planned to last 2 years. Up to 55 (up to 18 for the Phase I portion, up to 37 for the Phase II portion).

Further study details as provided by University of Southern California:

Primary Outcome Measures:

Clinical benefit defined as non-progression with no dose-limiting toxicity or other toxicity requiring termination of treatment [ Time Frame: At 3 months up to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to overall disease progression [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Response for patients with measurable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: At 3 months up to 24 months ] [ Designated as safety issue: No ]

To assess the prostate specific antigen (PSA) response rate in patients treated with AN-152 [ Time Frame: At 3 months up to 24 months ] [ Designated as safety issue: No ]

Time to PSA progression [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: At 3 weeks up to 72 weeks ] [ Designated as safety issue: Yes ]

Pain palliation defined as a 2-point decrease in pain scale of 1-10 without concomitant increase in analgesic medication use (Correlative study) [ Time Frame: At 3 weeks up to 72 weeks ] [ Designated as safety issue: No ]

Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Patients receive doxorubicin-GnRH agonist conjugate AEZS-108 intravenously (IV) over 2 hours once every 21 days (21 days = 1 cycle). Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Documented progression on (a) at least one prior hormone treatment, which must have incorporated luteinizing hormone-releasing hormone (LH- RH)agonist therapy AND (b) at least one chemotherapy regimen, which must have been taxane based

Progression may be demonstrated by PSA (defined by a 25% increase in the PSA from its most recent treatment nadir, confirmed with a second measurement at least 4 weeks later) or radiologic criteria (defined by radiologic documentation of a new lesion or a >= 20% increase in the sum of the diameters of previously noted measurable lesions)

Palliative radiation therapy (RT) for metastatic disease is allowed only if =< 25% of total body bone marrow was irradiated and =< 35Gy administered to the pericardial area

28 days must have elapsed since completion of RT with bone marrow recovery

Soft tissue disease irradiated in the prior 2 months may not be designated as measurable disease

Adequate hepatic function, defined by bilirubin =< 1.5 mg/dL AND alkaline phosphatase =< 3x ULN for the reference lab (=< 5x ULN for patients with known hepatic metastases and no limit for patients with known bone metastases) AND AST and ALT =< 3x ULN (=< 5x the ULN for patients with known hepatic metastases)

Must have recovered from acute and late effects of any prior surgery, radiotherapy or other anti-neoplastic therapy

Patients or their legal representatives must be able to read,understand, and provide informed consent

Men of childbearing potential must consent to use barrier contraception while on treatment and for 90 days thereafter

Willingness to discontinue LH-RH analogue therapy and for the duration of the study

Exclusion

Ongoing use of an LH-RH agonist (or antagonist)

Patients who agree to stop LH-RH agonist therapy will be eligible but may need to wait until their required washout period is over

Patients whose washout period is more than 6 weeks will not be eligible

Duration of washout period varies with the formulation of the LH-RH agonist being used and should be 2 weeks after the next dose would be scheduled. Specifically: a) For patients receiving a monthly formulations of LH-RH agonist, 6 weeks must pass from the last dose before eligibility; b) For patients receiving a 3-month depot formulation of LH-RH agonist, 14 weeks must pass from the last dose before eligibility; c) For patients receiving a 4- month depot formulation of LH-RH agonist, 18 weeks must pass from the last dose before eligibility; d) For patients receiving a 6- month depot formulation of LH-RH agonist, 26 weeks must pass from the last dose before eligibility; e) For patients with an annual LH-RH implant, 2 weeks must pass after removal of the implant before eligibility

Presence of an active infection or fever within 3 days of the first scheduled protocol treatment

Presence of parenchymal brain metastases

Patients with neurological symptoms must have a CT or magnetic resonance imaging (MRI)scan of the brain showing no metastases within 60 days of enrollment

History of prior malignancy within the past 5 years with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or superficial bladder

Patients with known hypersensitivity to any of the components of AN-152 including doxorubicin and LH-RH agonists

Patients who received radiotherapy within 4 weeks of entry

Patients who received treatment with strontium-89 or samarium-153 are excluded, except prior samarium will be allowed provided it was administered more than 1 year ago and/or the patient has demonstrated the ability to receive cytotoxic chemotherapy without excess of myelosuppression after receiving samarium.

Patients with a history of unstable or newly diagnosed angina pectoris, documented history of current serious arrhythmia or congestive heart failure or recent myocardial infarction (within 6 months of enrollment)

Left ventricular ejection fraction (EF) < 50%

Prior exposure to anthracyclines or anthracenediones including doxorubicin, daunorubicin, and mitoxantrone

Major surgery within the last 2 weeks

Receiving concurrent investigational therapy or have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication)

Known HIV or hepatitis B or C infection

Life expectancy < 3 months

Presence of any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with interpretation of the results

Prior treatment with AN-152

Lack of ability or willingness to give informed consent

Anticipated non-availability for study visits/procedures

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01240629